The present invention relates to the field of catalysts. More particularly, the invention relates to catalysts which are useful in enantioselective syntheses.
In recent years, catalytic transformations of organic diazo compounds have been used as highly versatile synthetic methods. Efficient procedures for the formation of carbon-carbon bonds by cyclopropanation, dipolar addition, carbon-hydrogen insertion, aromatic substitution reactions, and ylid generation/rearrangement with allylamines, allyl sulfides, and allyl ethers have been reported.
Electrophilic metal carbenes are produced from reactions of diazo compounds with transition metal complexes that possess an open coordination site. Among the catalysts that have been employed for carbenoid transformations, rhodium(II) carboxylates, which are resistant to ligand displacement, electron transfer reactions, and olefin complexation, have been found to be effective. Also, Rhodium(II) acetamide has recently been used for trans(anti) stereoselectivity enhancement in cyclopropanation reactions.
Only a limited number of chiral catalysts for metal carbene transformations have been reported. These chiral catalysts have been successfully employed only for cyclopropane syntheses. For example, Aratani et al. have prepared chiral Schiff base complexes of copper(II) such as that with the following structure: The use of this Aratani catalyst has yielded enantiomeric excesses (e.e.) as high as 90% in the synthesis of chrysanthemic acid esters. One such synthesis produces the following chrysanthemic acid ester with a 64% yield: 
Matlin et al. reported in 1984, the use of copper(II) complexes of 3-trifluoroacetyl-(+)-camphor for the asymmetric cyclopropanation of styrene with 2-diazodimedone. Although the enantiomerically pure cyclopropane product was obtained, its reported yield was only 48%.
Other chiral copper catalysts have also been reported. In particular, chiral catalysts have been prepared from Schiff bases derived from (S)-(−)-1-phenylethylamine, from binaphthyl-o, o′-diamines, from alpha amino alcohols, from amino acids, from amino esters, from amino sugars, and from tartaric acid. However, these chiral copper catalysts have only low to moderate reported enantiomeric excesses in cyclopropanation reactions.
Nakamura and Otsuka reported in 1978 the preparation of chiral bis(1,2)-dioximato)cobalt(II) complexes derived from d-camphor having the following structure (B=pyridine): Nakamura and Otsuka also reported the use of this catalyst for cyclopropanation of conjugated dienes, styrenes, and electron-deficient alkenes that include ethyl acrylate and acrylonitrile. Vinyl ethers and mono-olefins, including cyclohexene, do not react with diazo-esters under the influence of these catalysts, thus suggesting that the intermediate metal carbene possesses nucleophilic character. Optical yields in cyclopropanation reactions catalyzed by this catalyst are moderate. Although cyclopropane yields are ordinarily high, stereoselectivities are reportedly low.
In 1989, A. Pfaltz reported the synthesis and uses of (semicorrinato)copper catalysts for enantioselective cyclopropanation reactions: In the presence of these catalysts mono-substituted olefins react with diazo compounds to produce the corresponding cyclopropane derivatives in high optical yields. However, di- and tri-substituted olefins give low product yields.
Carbenoid insertion into the N-H bond of beta lactams has become a standard method for synthesis of carbapenam, oxapenam, carbacephem, and oxacephem systems. Rhodium(II) carboxylates have been used as the catalysts for these syntheses. An example is as follows: 